Research

Obesity represents a major health problem worldwide, especially in the western world. This condition is associated with chronic low-grade inflammation and cellular stress that negatively impacts insulin sensitivity and disrupts metabolic homeostasis. One of the primary organelle that is affected in obesity is the endoplasmic reticulum (ER). The ER comprises a network of membranes that plays an essential role in protein synthesis and folding and is the main Ca2+ reservoir of the cell. Under harmful conditions ER is unable to fold the proteins correctly, and the misfolded proteins accumulate in the ER lumen creating ER stress. This stress triggers a protective response, called the unfolded protein response (UPR). In obesity, ER stress is increased and the UPR is activated in adipose tissue and liver in experimental models and in humans. Another cellular organelle affected by stress conditions in obesity is the mitochondria, a dynamic organelle that plays a critical role in ATP production and apoptosis. Although ER and mitochondria have distinct roles in living cells, these organelles interact physically and functionally coordinating complex signaling mechanisms. Structural studies unveil that ER and mitochondria are physically linked in zones of close contact called mitochondria associated ER-membranes (MAM). This association has pivotal roles in several cellular functions, including Ca2+ signaling, lipid transport, energy metabolism and cellular survival. MAM is enriched in proteins such as IP3 Ca2+ channel, molecular chaperones such as calnexin, calreticulin and GRP75. My research is focused on investigating whether obesity alters the physical communication between ER and mitochondria and if in this condition, ER stress could be linked to mitochondria dysfunction in metabolic tissues such as liver.

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